Post-translational modifications are chemical changes to a protein that occur after ribosomes have translated its primary structure. Post-translational modifications include, but are not limited to, glycation, phosphorylation, lipoylation, citrullination (e.g., in rheumatoid arthritis), hypusination (e.g., in diabetic inflammation), transglutamination (e.g., in celiac disease), and sumoylation (e.g., in cancer, neurodegenerative disease, and heart disease). Post-translational modifications influence protein behavior. For example, the post-translational addition or removal of phosphate moieties from proteins plays a regulatory role in many biochemical pathways and signal transduction pathways.
Numerous diseases inflicted or associated with post-translationally modified (PTM) proteins that are difficult to obtain in homogenous form. As such, PTM proteins could be used as biomarkers, namely diagnostic, prognostic and treatment monitoring tools in assessing the disease state of patients. Shortages of such endogenous PTM proteins can impede or prevent a convenient means to analyze PTM proteins. Thus, there is an unmet need to obtain synthetic constructs that can function as effective surrogates of endogenous PTM proteins. Such surrogates could be prepared in homogenous form to replace endogenous PTM proteins and serve as convenient standards, calibrators, and/or reference compounds that facilitate the detection and analysis of endogenous PTM proteins. Such surrogates could further be used to diagnose or monitor the progression of and/or efficacy of treatment of diseases associated with PTM proteins.
Diabetes mellitus (diabetes) is one such disease for which PTM proteins are well characterized. Diabetes is a leading cause of morbidity and mortality in the adult population. This is primarily because diabetic patients tend to develop vascular complications that involve the kidneys (diabetic nephropathy), the retina (diabetic retinopathy), as well as large and small blood vessels in other organs (macro- and microvascular disease) including nerves (diabetic neuropathy). It is well established that the vascular complications of diabetes are caused by elevated blood glucose levels over long periods of time. Elevated blood glucose levels contribute to the glycation of proteins. Glycation, the non-enzymatic covalent attachment of glucose to proteins, is considered a major post-translational modification causing tissue damage in diabetic subjects. Glycation involves the reaction of glucose and/or other reducing sugars with amino groups in proteins resulting in the formation of a Schiff's base or aldimine. This labile Schiff's base can cyclize to a more stable glycosylamine or rearrange and cyclize to Amadori adducts as shown below.

The function of the glycated protein may be impaired, depending on the location of the amino groups affected. Glycation of key regulatory proteins, such as those which prevent activation of the complement system (e.g., CD59), is believed to contribute to the clinical complications of diabetes mellitus. Thus, compositions and methods which help measure the extent of protein glycation of key regulatory proteins of the complement system such as CD59 are considered valuable clinical tools to detect prediabetics and diabetics, assess glycemic control and the efficacy of diabetes treatment.